The clinical profile of NMOSD in Australia and New Zealand.

Neuromyelitis optica spectrum disorders (NMOSD) are an inflammation of the central nervous system associated with autoantibodies to aquaporin-4. We have undertaken a clinic-based survey of NMOSD in the Australia and New Zealand populations with the aim of characterising the clinical features and establishing the value of recently revised diagnostic criteria. Cases of possible NMOSD and age and sex-matched controls with multiple sclerosis (MS) were referred from centres across Australia and New Zealand.

Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient.

Objective: Autoimmune encephalitis (AE) is an important and treatable cause of acute encephalitis. Diagnosis of AE in a developing child is challenging because of overlap in clinical presentations with other diseases and complexity of normal behavior changes. Existing diagnostic criteria for adult AE require modification to be applied to children, who differ from adults in their clinical presentations, paraclinical findings, autoantibody profiles, treatment response, and long-term outcomes.

Levetiracetam efficacy in PCDH19 Girls Clustering Epilepsy.

Background: PCDH19 Girls clustering epilepsy (GCE) has a phenotypic spectrum that includes developmental and epileptic encephalopathy. PCDH19-GCE presents with clusters of seizures in the first years of life. Although patients typically outgrow their seizures, many are left with intellectual disability.

Identification of Novel Pathways Associated with Patterned Cerebellar Purkinje Neuron Degeneration in Niemann-Pick Disease, Type C1.

Niemann-Pick disease, type C1 (NPC1) is a lysosomal disease characterized by progressive cerebellar ataxia. In NPC1, a defect in cholesterol transport leads to endolysosomal storage of cholesterol and decreased cholesterol bioavailability. Purkinje neurons are sensitive to the loss of NPC1 function.

Neuromyelitis Optica Spectrum Disorder and Anti-Aquaporin 4 Channel Immunoglobulin in an Australian Pediatric Demyelination Cohort.

Neuromyelitis optica spectrum disorder is uncommon in children, and often seronegative for aquaporin-4 immunoglobulin G (AQP4-IgG). We conducted a retrospective study of 67 children presenting to a single Australian center with acquired demyelinating syndromes over a 7-year period. All patients were tested for AQP4-IgG.

Yield of comparative genomic hybridization microarray in pediatric neurology practice.

Objective: The present study investigated the diagnostic yield of array comparative genomic hybridization (aCGH) in a large cohort of children with diverse neurologic disorders as seen in child neurology practice to test whether pathogenic copy number variants (CNVs) were more likely to be detected in specific neurologic phenotypes.

Methods: A retrospective cross-sectional analysis was performed on 555 children in whom a genetic etiology was suspected and who underwent whole-genome aCGH testing between 2006 and 2012. Neurologic phenotyping was performed using hospital medical records.

Is there a role for arcing techniques in proton therapy?

Proton arc therapy (PAT) has been proposed as a possible evolution for proton therapy. This commentary uses dosimetric and cancer risk evaluations from earlier studies to compare PAT with intensity modulated proton therapy. It is concluded that, although PAT may not produce better physical dose distributions than intensity modulated proton therapy, the radiobiological considerations associated with particular PAT techniques could offer the possibility of an increased therapeutic index.

Metabolic Syndrome Rather Than Body Mass Index Is Associated With Treatment Response to Ketamine Infusions.

Purpose: There is a practical need for the identification of pretreatment clinical and epidemiological response predictors to repeat ketamine infusions. Response predictors can serve to guide clinical inclusion of patients and weigh risks versus benefits for those receiving maintenance ketamine. Previous studies indicate a link between obesity, depression, and treatment response.

Clinical and neuroimaging phenotypes of genetic parkinsonism from infancy to adolescence.

Genetic early-onset parkinsonism presenting from infancy to adolescence (≤21 years old) is a clinically diverse syndrome often combined with other hyperkinetic movement disorders, neurological and imaging abnormalities. The syndrome is genetically heterogeneous, with many causative genes already known. With the increased use of next-generation sequencing in clinical practice, there have been novel and unexpected insights into phenotype-genotype correlations and the discovery of new disease-causing genes.

An Acute Pain Service experience initiating methadone for opioid use disorder in hospitalized patients with acute pain.

Objective: Inform readers of the use of a clinical pathway that includes initiation of methadone in hospitalized patients with acute pain who have untreated opioid use disorder (OUD).

Design: A retrospective chart review with frequency distributions and descriptive statistics calculated to describe demo-graphic and clinical characteristics of the sample.

Setting: Urban academic hospital.

Causes and Clinical Features of Childhood Encephalitis: A Multicenter, Prospective Cohort Study.

Background: We aimed to determine the contemporary causes, clinical features, and short-term outcome of encephalitis in Australian children.

Methods: We prospectively identified children (≤14 years of age) admitted with suspected encephalitis at 5 major pediatric hospitals nationally between May 2013 and December 2016 using the Paediatric Active Enhanced Disease Surveillance (PAEDS) Network. A multidisciplinary expert panel reviewed cases and categorized them using published definitions.

The NEO-FFI domain of openness to experience moderates ketamine response in treatment resistant depression.

Background: There are many putative mechanisms by which ketamine has its effect and many unanswered questions about risks and benefits of long-term ketamine therapy. A research imperative is the identification of predictors of response to intravenous ketamine, especially a sustained response to maintenance ketamine. Temperament is an inherited aspect of personality and is a predictive factor for outcome in treatment resistant depressed (TRD) patients.

Sensory dysregulation in tic disorders is associated with executive dysfunction and comorbidities.

Background: Tics are conceptualized as a sensorimotor phenomenon with a premonitory urge typically described by patients. As observed in other neurodevelopmental disorders, we have observed sensory dysregulation symptoms, such as tactile hypersensitivity to clothing, in children with tic disorders; however, formal clinical research in this area is limited.

Objective: To define the presence of sensory dysregulation symptoms in tic disorders, and their clinical associations.

Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination.

Over recent years, human autoantibodies targeting myelin oligodendrocyte glycoprotein (MOG Ab) have been associated with monophasic and relapsing central nervous system demyelination involving the optic nerves, spinal cord, and brain. While the clinical relevance of MOG Ab detection is becoming increasingly clear as therapeutic and prognostic differences from multiple sclerosis are acknowledged, an in-depth characterization of human MOG Ab is required to answer key challenges in patient diagnosis, treatment, and prognosis. Herein, we investigated the epitope, binding sensitivity, and affinity of MOG Ab in a cohort of 139 and 148 MOG antibody-seropositive children and adults (n = 287 patients at baseline, 130 longitudinal samples, and 22 cerebrospinal fluid samples).

Neuropsychological outcomes of childhood acute necrotizing encephalopathy.

Acute necrotizing encephalopathy (ANE) is a rare form of acute encephalopathy, predominantly occurring in childhood, which has a typical radiological phenotype including bilateral, symmetrical, diffusion-restricted lesions of the thalami; posterior putamen; cerebellum; and brainstem. To date, no study has systematically examined the long-term cognitive and psychological impact of ANE. The current study describes the neuropsychological outcomes of three paediatric cases of ANE, ranging from 18 months to 10 years post ANE.

Acute Hemorrhagic Leukoencephalopathy: Pathological Features and Cerebrospinal Fluid Cytokine Profiles.

Background: Acute hemorrhagic leukoencephalopathy is a rare encephalopathy of unknown etiology, causing fulminant, hemorrhagic central nervous system demyelination with high mortality. It is unclear whether acute hemorrhagic leukoencephalopathy is an entirely distinct entity from acute disseminated encephalomyelitis.

Patients And Methods: We report two patients with rapidly progressive neurological illness resulting in raised intracranial pressure and coma, with biopsy-proven acute hemorrhagic leukoencephalopathy (perivascular hemorrhages and demyelination, predominantly neutrophil infiltrates).

Etiology is the key determinant of neuroinflammation in epilepsy: Elevation of cerebrospinal fluid cytokines and chemokines in febrile infection-related epilepsy syndrome and febrile status epilepticus.

Objective: To investigate intrathecal inflammation using cerebrospinal fluid (CSF) cytokines and chemokines in a subgroup of pediatric epilepsy patients with frequent daily seizures.

Methods: We measured 32 cytokines/chemokines using multiplex immunoassay in CSF collected from pediatric patients with febrile infection-related epilepsy syndrome (FIRES)/FIRES-related disorders (FRD; n = 6), febrile status epilepticus (FSE; n = 8), afebrile status epilepticus (ASE; n = 8), and chronic epilepsy with frequent daily seizures (n = 21) and compared the results with noninflammatory neurological disorders (NIND; n = 20) and encephalitis (n = 43). We also performed longitudinal CSF cytokine/chemokine studies in three cases with FIRES/FRD.

Elephants have a nose for quantity.

Animals often face situations that require making decisions based on quantity. Many species, including humans, rely on an ability to differentiate between more and less to make judgments about social relationships, territories, and food. Habitat-related choices require animals to decide between areas with greater and lesser quantities of food while also weighing relative risk of danger based on group size and predation risk.

Non-Steady State Analysis of Enzyme Kinetics in Real Time Elucidates Substrate Association and Dissociation Rates: Demonstration with Analysis of Firefly Luciferase Mutants.

Firefly luciferase has been widely used in biotechnology and biophotonics due to photon emission during enzymatic activity. In the past, the effect of amino acid substitutions (mutants) on the enzymatic activity of firefly luciferase has been characterized by the Michaelis constant, K. The K is obtained by plotting the maximum relative luminescence units (RLU) detected for several concentrations of the substrate (luciferin or luciferyl-adenylate).

Anchoring cortical granules in the cortex ensures trafficking to the plasma membrane for post-fertilization exocytosis.

Following fertilization, cortical granules exocytose ovastacin, a metalloendopeptidase that cleaves ZP2 in the zona pellucida surrounding mouse eggs to prevent additional sperm binding. Using high- and super-resolution imaging with ovastacin as a fluorescent marker, we characterize cortical granule dynamics at single granule resolution in transgenic mouse eggs. Newly-developed imaging protocols provide an unprecedented view of vesicular dynamics near the plasma membrane in mouse eggs.